LIVER CIRRHOSIS

BIOLOGY PROJECT

Under the Guidance of: Submitted By:

Mrs.SUNEETA JOHANSTIN.C
S1601339
XII B

Kovaipudur,
Coimbatore - 42.
(AFFILIATED TO CBSE, NEW DELHI)
 BATCH 2020-2021

LIVER CIRRHOSIS

1) Introduction and Overview:

Cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases
and conditions, such as hepatitis and chronic alcoholism. Cirrhosis, also known as liver cirrhosis or
hepatic cirrhosis, is a condition in which the liver does not function properly due to long-term damage.
Each time when the liver is injured — whether by disease, excessive alcohol consumption or another
cause — it tries to repair itself. In the process, scar tissue forms. As cirrhosis progresses, more and more
scar tissue forms, making it difficult for the liver to function (decompensated cirrhosis). Advanced
cirrhosis is life-threatening. The liver damage done by cirrhosis generally can't be undone. But if liver
cirrhosis is diagnosed early and the cause is treated, further damage can be limited and, rarely, reversed.

Specialty area: Gastroenterology

Other names of this disease are

 Cirrhosis of the liver

 Hepatic cirrhosis
 Hepatic failure

The abdomen of a person with cirrhosis showing massive fluid buildup and very visible veins
Pronunciation is shown below
2) Signs and Symptoms:

Cirrhosis often has no signs or symptoms until liver damage is extensive. When signs and symptoms
do occur, they may include:

 Fatigue
 Easily bleeding or bruising
 Loss of appetite
 Nausea
 Swelling in legs, feet or ankles (edema)
 Weight loss
 Itchy skin
 Yellow discoloration in the skin and eyes (jaundice)
 Fluid accumulation in abdomen (ascites)
 Spiderlike blood vessels on skin
 Redness in the palms of the hands
 For women, absent or loss of periods not related to menopause
 For men, loss of sex drive, breast enlargement (gynecomastia) or testicular atrophy
 Confusion, drowsiness and slurred speech (hepatic encephalopathy)

The difference between the Normal liver and liver affected with cirrhosis is shown below;
3) Liver dysfunction:

The following features are as a direct consequence of liver cells not functioning.

 Spider angiomata or spider nevi are vascular lesions consisting of a central arteriole surrounded
by many smaller vessels (hence the name "spider") and occur due to an increase in estradiol.
One study found that spider angiomata occur in about 1/3 of cases.
 Palmar erythema is a reddening of palms at the thenar and hypothenar eminences also as a
result of increased estrogen.
 Gynecomastia, or increase in breast gland size in men that is not cancerous, is caused by
increased estradiol and can occur in up to 2/3 of patients. This is different from increase in
breast fat in overweight people.
 Hypogonadism, a decrease in male sex hormones may manifest as impotence, infertility, loss of
sexual drive, and testicular atrophy, and can result from primary gonadal injury or suppression
of hypothalamic/pituitary function. Hypogonadism is associated with cirrhosis due to alcoholism
or hemochromatosis.
 Liver size can be enlarged, normal, or shrunken in people with cirrhosis.
 Ascites, accumulation of fluid in the peritoneal cavity (space in the abdomen), gives rise to "flank
dullness". This may be visible as an increase in abdominal girth.
 Fetor hepaticus is a musty breath odor resulting from increased dimethyl sulfide.
 Jaundice, or icterus, is yellow discoloration of the skin and mucous membranes (with the white
of the eye being especially noticeable) due to increased bilirubin (at least 2–3 mg/dl or 30
µmol/l). The urine may also appear dark.
 Portal hypertension
 Liver cirrhosis increases resistance to blood flow and leads to higher pressure in the portal
venous system, resulting in portal hypertension. Effects of portal hypertension include:
 Splenomegaly (increase in size of the spleen) is found in 35% to 50% of patients.
 Esophageal varices result from collateral portal blood flow through vessels in the stomach
and esophagus (a process called portacaval anastomosis). When these blood vessels
become enlarged, they are called varices and are more likely to rupture. Variceal rupture
often leads to severe bleeding, which can prove fatal.
  Caput medusae are dilated periumbilical collateral veins due to portal hypertension. Blood
from the portal venous system may be shunted through the periumbilical veins and
ultimately to the abdominal wall veins, manifesting as a pattern that may resemble the head
of Medusa.
 Cruveilhier-Baumgarten bruit is a venous hum heard in the epigastric region (on
examination by stethoscope) due to collateral connections forming between the portal
system and the periumbilical veins as a result of portal hypertension.

4) Causes:

A wide range of diseases and conditions can damage the liver and lead to cirrhosis.

Some of the causes include:

 Chronic alcohol abuse

 Chronic viral hepatitis (hepatitis B, C and D)
 Fat accumulating in the liver (nonalcoholic fatty liver disease)
 Iron buildup in the body (hemochromatosis)
 Cystic fibrosis
 Copper accumulated in the liver (Wilson's disease)
 Poorly formed bile ducts (biliary atresia)
 Alpha-1 antitrypsin deficiency
 Inherited disorders of sugar metabolism (galactosemia or glycogen storage disease)
 Genetic digestive disorder (Alagille syndrome)
 Liver disease caused by body's immune system (autoimmune hepatitis)
 Destruction of the bile ducts (primary biliary cirrhosis)
 Hardening and scarring of the bile ducts (primary sclerosing cholangitis
 Infection, such as syphilis or brucellosis
 Medications, including methotrexate or isoniazid

Some of the unestablished causes listed below;

There are some changes seen in cirrhosis whose causes are not clearly known. They may also be
a sign of other non-liver related causes.

 Nail changes.
 Muehrcke's lines – paired horizontal bands separated by normal color resulting from
hypoalbuminemia (inadequate production of albumin). It is not specific for cirrhosis.
 Terry's nails – proximal two-thirds of the nail plate appears white with distal one-third red,
also due to hypoalbuminemia.
 Clubbing – angle between the nail plate and proximal nail fold > 180 degrees. It is not
specific for cirrhosis and can therefore be due to a number of conditions.
 Hypertrophic osteoarthropathy. Chronic proliferative periostitis of the long bones that can cause
considerable pain. It is not specific for cirrhosis.
 Dupuytren's contracture. Thickening and shortening of palmar fascia (tissue on the palm of the
hands) that leads to flexion deformities of the fingers. Caused by fibroblastic proliferation
(increased growth) and disorderly collagen deposition. It is relatively common (33% of patients).
5) Risk factors:

 Drinking too much alcohol. Excessive alcohol consumption is a risk factor for cirrhosis.
 Being overweight. Being obese increases risk of conditions that may lead to cirrhosis, such as
nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
 Having viral hepatitis. Not everyone with chronic hepatitis will develop cirrhosis, but it's one of
the world's leading causes of liver disease.

6) Complications:

Complications of cirrhosis can include:

 High blood pressure in the veins that supply the liver (portal hypertension). Cirrhosis slows the
normal flow of blood through the liver, thus increasing pressure in the vein that brings blood to
the liver from the intestines and spleen.
 Swelling in the legs and abdomen. The increased pressure in the portal vein can cause fluid to
accumulate in the legs (edema) and in the abdomen (ascites). Edema and ascites also may result
from the inability of the liver to make enough of certain blood proteins, such as albumin.
 Enlargement of the spleen (splenomegaly). Portal hypertension can also cause changes to and
swelling of the spleen, and trapping of white blood cells and platelets. Decreased white blood
cells and platelets in your blood can be the first sign of cirrhosis.
 Bleeding. Portal hypertension can cause blood to be redirected to smaller veins. Strained by
the extra pressure, these smaller veins can burst, causing serious bleeding. Portal hypertension
may cause enlarged veins (varices) in the esophagus (esophageal varices) or the stomach (gastric
varices) and lead to life-threatening bleeding. If the liver can't make enough clotting factors, this
also can contribute to continued bleeding.
 Infections. If you have cirrhosis, your body may have difficulty fighting infections. Ascites can
lead to bacterial peritonitis, a serious infection.
 Malnutrition. Cirrhosis may make it more difficult for your body to process nutrients, leading
to weakness and weight loss.
 Buildup of toxins in the brain (hepatic encephalopathy). A liver damaged by cirrhosis isn't
able to clear toxins from the blood as well as a healthy liver can. These toxins can then build up
in the brain and cause mental confusion and difficulty concentrating. With time, hepatic
encephalopathy can progress to unresponsiveness or coma.
 Jaundice. Jaundice occurs when the diseased liver doesn't remove enough bilirubin, a blood
waste product, from your blood. Jaundice causes yellowing of the skin and whites of the eyes
and darkening of urine.
 Bone disease. Some people with cirrhosis lose bone strength and are at greater risk of
fractures.
 Increased risk of liver cancer. A large proportion of people who develop liver cancer have pre-
existing cirrhosis.
 Acute-on-chronic cirrhosis. Some people end up experiencing multiorgan failure. Researchers
now believe this is a distinct complication in some people who have cirrhosis, but they don't
fully understand its causes.

7) Prevention:
 Reduce the risk of cirrhosis by taking the following steps to care for the liver:

 Do not drink alcohol if you have cirrhosis. If you have liver disease, you should avoid alcohol.
 Eat a healthy diet. Choose a plant-based diet that's full of fruits and vegetables. Select whole
grains and lean sources of protein. Reduce the amount of fatty and fried foods you eat.
 Maintain a healthy weight. An excess amount of body fat can damage your liver. Talk to your
doctor about a weight-loss plan if you are obese or overweight.
 Reduce your risk of hepatitis. Sharing needles and having unprotected sex can increase your risk
of hepatitis B and C. Ask your doctor about hepatitis vaccinations.

8) Diagnosis:

 Micrograph showing cirrhosis. Trichrome stain.

The gold standard for diagnosis of cirrhosis is a liver biopsy, through a percutaneous,
transjugular, laparoscopic, or fine-needle approach. A biopsy is not necessary if the clinical,
laboratory, and radiologic data suggests cirrhosis. Furthermore, there is a small but significant
risk of complications from liver biopsy, and cirrhosis itself predisposes for complications caused
by liver biopsy.

 Lab findings.

The following findings are typical in cirrhosis:

 Thrombocytopenia – typically multifactorial. Due to alcoholic marrow suppression, sepsis,

lack of folate, platelet sequestering in the spleen as well as decreased thrombopoietin.
However, this rarely results in a platelet count < 50 000/mL.
 Aminotransferases – AST and ALT are moderately elevated, with AST > ALT. However,
normal aminotransferase levels do not preclude cirrhosis.
 Alkaline phosphatase – slightly elevated but less than 2–3 times the upper limit of normal.
 Gamma-glutamyl transferase – correlates with AP levels. Typically much higher in chronic
liver disease from alcohol.
 Bilirubin – levels normal when compensated but may elevate as cirrhosis progresses.
 Albumin – levels fall as the synthetic function of the liver declines with worsening cirrhosis,
since albumin is exclusively synthesized in the liver
 Prothrombin time – increases, since the liver synthesizes clotting factors.
 Globulins – increased due to shunting of bacterial antigens away from the liver to lymphoid
tissue.
 Serum sodium – hyponatremia due to inability to excrete free water resulting from high
levels of ADH and aldosterone.
 Leukopenia and neutropenia – due to splenomegaly with splenic margination.
 Coagulation defects – the liver produces most of the coagulation factors and thus
coagulopathy correlates with worsening liver disease.
 Glucagon – increased in cirrhosis
 Vasoactive intestinal peptide – increased as blood is shunted in the intestinal system
because of portal hypertension
  Vasodilators – increased (such as nitric oxide and carbon monoxide) reducing afterload with
compensatory increase in cardiac output, mixed venous oxygen saturation
 Renin – increased (as well as sodium retention in kidneys) secondary to fall in systemic
vascular resistance
 FibroTest is a biomarker for fibrosis that can be done instead of a biopsy.
 Other laboratory studies performed in newly diagnosed cirrhosis may include:
 Serology for hepatitis viruses, autoantibodies (ANA, anti-smooth muscle, anti-mitochondria,
anti-LKM)
 Ferritin and transferrin saturation: markers of iron overload as in hemochromatosis, copper
and ceruloplasmin: markers of copper overload as in Wilson's disease
 Immunoglobulin levels (IgG, IgM, IgA) – these immunoglobins are non-specific, but may help
in distinguishing various causes
 Cholesterol and glucose
 Alpha 1-antitrypsin
 Imaging;
 Doppler ultrasonography of the portal vein over 5 seconds, showing peaks of maximal
velocity, as well as points of minimal velocity.
 Ultrasound is routinely used in the evaluation of cirrhosis. It may show a small and nodular
liver in advanced cirrhosis along with increased echogenicity with irregular appearing areas.
Other liver findings suggestive of cirrhosis in imaging are an enlarged caudate lobe, widening
of the fissures and enlargement of the spleen. An enlarged spleen (splenomegaly), which
normally measures less than 11–12 cm in adults, can be seen and may suggest underlying
portal hypertension. Ultrasound may also screen for hepatocellular carcinoma, portal
hypertension, and Budd-Chiari syndrome (by assessing flow in the hepatic vein). An
increased portal vein pulsatility is an indicator of cirrhosis, but may also be caused by an
increased right atrial pressure.
 Cirrhosis is diagnosed with a variety of elastography techniques. Because a cirrhotic liver is
generally stiffer than a healthy one, imaging the liver's stiffness can give diagnostic
information about the location and severity of cirrhosis. Techniques used include transient
elastography, acoustic radiation force impulse imaging, supersonic shear imaging and
magnetic resonance elastography. Compared to a biopsy, elastography can sample a much
larger area and is painless. It shows a reasonable correlation with the severity of cirrhosis.

 Other tests performed in particular circumstances include abdominal CT and liver/bile duct MRI
(MRCP).
 Liver cirrhosis with ascites
 Liver cirrhosis as seen on a CT of the abdomen in transverse orientation
 caudate lobe hypertrophy in ultrasound due to cirrhosis
 Hepatofugal flow in portal vein in ultrasound
 Endoscopy
 Gastroscopy (endoscopic examination of the esophagus, stomach, and duodenum) is
performed in patients with established cirrhosis to exclude the possibility of esophageal
 varices. If these are found, prophylactic local therapy may be applied (sclerotherapy or
banding) and beta blocker treatment may be commenced.
 Rarely are diseases of the bile ducts, such as primary sclerosing cholangitis, causes of
cirrhosis. Imaging of the bile ducts, such as ERCP or MRCP (MRI of biliary tract and pancreas)
may aid in the diagnosis.
 Pathology
 Macroscopically, the liver is initially enlarged, but with the progression of the disease, it
becomes smaller. Its surface is irregular, the consistency is firm, and the color is often yellow
(if associated with steatosis). Depending on the size of the nodules, there are three
macroscopic types: micronodular, macronodular, and mixed cirrhosis. In the micronodular
form (Laennec's cirrhosis or portal cirrhosis), regenerating nodules are under 3 mm. In
macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. Mixed
cirrhosis consists of nodules of different sizes.
 Micronodular cirrhosis, with diffuse areas of pallor.
 Pale macronodules of cirrhosis.
 Cirrhosis leading to hepatocellular carcinoma (autopsy specimen)
 However, cirrhosis is defined by its pathological features on microscopy: (1) the presence of
regenerating nodules of hepatocytes and (2) the presence of fibrosis, or the deposition of
connective tissue between these nodules. The pattern of fibrosis seen can depend on the
underlying insult that led to cirrhosis. Fibrosis can also proliferate even if the underlying
process that caused it has resolved or ceased. The fibrosis in cirrhosis can lead to
destruction of other normal tissues in the liver: including the sinusoids, the space of Disse,
and other vascular structures, which leads to altered resistance to blood flow in the liver,
and portal hypertension.

 Grading
 The severity of cirrhosis is commonly classified with the Child-Pugh score. This scoring
system uses bilirubin, albumin, INR, the presence and severity of ascites, and
encephalopathy to classify patients into class A, B, or C. Class A has a favourable prognosis,
while class C is at high risk of death. This system was devised in 1964 by Child and Turcotte,
and modified in 1973 by Pugh and others.
 More modern scores, used in the allocation of liver transplants but also in other contexts,
are the Model for End-Stage Liver Disease (MELD) score and its pediatric counterpart, the
Pediatric End-Stage Liver Disease (PELD) score.
 The hepatic venous pressure gradient, (difference in venous pressure between afferent and
efferent blood to the liver) also determines the severity of cirrhosis, although it is hard to
measure. A value of 16 mm or more means a greatly increased risk of death

9) Treatment:

Generally, liver damage from cirrhosis cannot be reversed, but treatment can stop or delay
further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an
energy-consuming process. Close follow-up is often necessary. Antibiotics are prescribed for infections,
and various medications can help with itching. Laxatives, such as lactulose, decrease the risk of
constipation; their role in preventing encephalopathy is limited.
  Preventing further liver damage

Regardless of the underlying cause of cirrhosis, consumption of alcohol and paracetamol

(acetaminophen), as well as other potentially damaging substances, are discouraged. Vaccination of
susceptible patients should be considered for Hepatitis A and Hepatitis B. Treating the cause of
cirrhosis prevents further damage; for example, giving oral antivirals such as entecavir and tenofovir
in patients of cirrhosis due to Hepatitis B prevents progression of cirrhosis. Similarly, control of
weight and diabetes prevents deterioration in cirrhosis due to Non-alcoholic steatohepatitis.

 Transplantation

If complications cannot be controlled or when the liver ceases functioning, liver

transplantation is necessary. Survival from liver transplantation has been improving over the 1990s,
and the five-year survival rate is now around 80%. The survival rate depends largely on the severity
of disease and other medical risk factors in the recipient.

 Decompensated cirrhosis

Manifestations of decompensation in cirrhosis include gastrointestinal bleeding, hepatic

encephalopathy (HE), jaundice or ascites. In patients with previously stable cirrhosis,
decompensation may occur due to various causes, such as constipation, infection (of any source),
increased alcohol intake, medication, bleeding from esophageal varices or dehydration. It may take
the form of any of the complications of cirrhosis listed below.

People with decompensated cirrhosis generally require admission to a hospital, with close
monitoring of the fluid balance, mental status, and emphasis on adequate nutrition and medical
treatment – often with diuretics, antibiotics, laxatives or enemas, thiamine and occasionally
steroids, acetylcysteine and pentoxifylline. Administration of saline is avoided, as it would add to the
already high total body sodium content that typically occurs in cirrhosis. Life expectancy without
liver transplant is low, at most 3 years.

 Palliative care

Palliative care is specialized medical care that focuses on providing patients with relief
from the symptoms, pain, and stress of a serious illness, such as cirrhosis. The goal of palliative
care is to improve quality of life for both the patient and the patient's family and it is
appropriate at any stage and for any type of cirrhosis.

Especially in the later stages, people with cirrhosis experience significant symptoms such
as abdominal swelling, itching, leg edema, and chronic abdominal pain which would be
amenable for treatment through palliative care. Because the disease is not curable without a
transplant, palliative care can also help with discussions regarding the person's wishes
concerning health care power of attorney, Do Not Resuscitate decisions and life support, and
potentially hospice. Despite proven benefit, people with cirrhosis are rarely referred to palliative
care.

10) Case Study and Medical history / Records:

 I have opted the above disease liver cirrhosis for my study purpose just because I have
personally seen and interacted with one of my uncle Mr.D.Aaron who was affected by this disease. He
developed the same type of symptoms discussed above and diagnosed for liver cirrhosis. He survived
only for just 12 month from the day of diagonisation of this disease. I have attached a few investigation
reports of him along with this assignment.